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A Strategy for Precise Treatment of Cardiac Malignant Neoplasms

View Article: PubMed Central - PubMed

ABSTRACT

The prevalence of cardiac malignant neoplasms in the general population has been shown to be significant higher than what was previously estimated, yet their treatment has remained difficult and effective therapies are lacking. In the current study, we developed a novel thermotherapy in which PEG-functionalized carbon nanotubes were injected into the tumor regions to assist in the targeted delivery of infrared radiation energy with minimal hyperthermic damage to the surrounding normal tissues. In a mouse model of cardiac malignant neoplasms, the injected carbon nanotubes could rapidly induce coagulative necrosis of tumor tissues when exposed to infrared irradiation. In accordance, the treatment was also found to result in a restoration of heart functions and a concomitant increase of survival rate in mice. Taken together, our carbon nanotube-based thermotherapy successfully addressed the difficulty facing conventional laser ablation methods with regard to off-target thermal injury, and could pave the way for the development of more effective therapies against cardiac malignant neoplasms.

No MeSH data available.


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Structural and functional characterization of single-walled carbon nanotubes.(a) TEM image of the synthesized carbon nanotubes; (b) Dispersion of carbon nanotubes in a stable aqueous suspension; (c) Size distribution of the carbon nanotubes as determined by a laser particle analyzer; (d) Internalization of green-fluorescent carbon nanotubes by NCI-H460 cells; (e) Carbon nanotubes exhibited no detectable cytotoxicity in the absence of laser treatment; (f) Exposure of carbon nanotube-treated cells to laser irradiation significantly reduced the number of viable cells. Abbreviation: TDI, transmitted detector integration; FITC, fluorescein isothiocyanate.
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f1: Structural and functional characterization of single-walled carbon nanotubes.(a) TEM image of the synthesized carbon nanotubes; (b) Dispersion of carbon nanotubes in a stable aqueous suspension; (c) Size distribution of the carbon nanotubes as determined by a laser particle analyzer; (d) Internalization of green-fluorescent carbon nanotubes by NCI-H460 cells; (e) Carbon nanotubes exhibited no detectable cytotoxicity in the absence of laser treatment; (f) Exposure of carbon nanotube-treated cells to laser irradiation significantly reduced the number of viable cells. Abbreviation: TDI, transmitted detector integration; FITC, fluorescein isothiocyanate.

Mentions: The synthesized carbon nanotubes were indicated by TEM imaging to comprise a single layer of graphene wall (Fig. 1a). PEG modification was found to significantly improve the dispersion and reduce the aggregation tendency of the carbon nanotubes in aqueous solution over the 7-day observation period (Fig. 1b). After phacofragmentation and surface modification, the final average size of the carbon nanotubes was approximately 50 nm (Fig. 1c). The uptake assay was performed by incubating FITC/PEG-conjugated carbon nanotubes with NCI-H460, a human lung cancer cell line, and subsequently visualizing cell distribution via confocal microscopy. The images confirmed that the nanotubes were mostly internalized or strongly adhered to the cell surface within four hours following the incubation (Fig. 1d). We next performed cell viability assays using CCK-8 kit to examine the anti-cancer effect of laser irradiation and carbon nanotubes in vitro. As illustrated in Fig. 1e, incubating the cells with carbon nanotubes in the absence of laser exposure did not induce apoptosis (P = 0.021). On the other hand, the cancer cells incubated with carbon nanotubes showed reduced viability only when subjected to laser treatment, as indicated by the sharp decrease of fluorescence at 450 nm. (P = 0.021, Fig. 1f).


A Strategy for Precise Treatment of Cardiac Malignant Neoplasms
Structural and functional characterization of single-walled carbon nanotubes.(a) TEM image of the synthesized carbon nanotubes; (b) Dispersion of carbon nanotubes in a stable aqueous suspension; (c) Size distribution of the carbon nanotubes as determined by a laser particle analyzer; (d) Internalization of green-fluorescent carbon nanotubes by NCI-H460 cells; (e) Carbon nanotubes exhibited no detectable cytotoxicity in the absence of laser treatment; (f) Exposure of carbon nanotube-treated cells to laser irradiation significantly reduced the number of viable cells. Abbreviation: TDI, transmitted detector integration; FITC, fluorescein isothiocyanate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385561&req=5

f1: Structural and functional characterization of single-walled carbon nanotubes.(a) TEM image of the synthesized carbon nanotubes; (b) Dispersion of carbon nanotubes in a stable aqueous suspension; (c) Size distribution of the carbon nanotubes as determined by a laser particle analyzer; (d) Internalization of green-fluorescent carbon nanotubes by NCI-H460 cells; (e) Carbon nanotubes exhibited no detectable cytotoxicity in the absence of laser treatment; (f) Exposure of carbon nanotube-treated cells to laser irradiation significantly reduced the number of viable cells. Abbreviation: TDI, transmitted detector integration; FITC, fluorescein isothiocyanate.
Mentions: The synthesized carbon nanotubes were indicated by TEM imaging to comprise a single layer of graphene wall (Fig. 1a). PEG modification was found to significantly improve the dispersion and reduce the aggregation tendency of the carbon nanotubes in aqueous solution over the 7-day observation period (Fig. 1b). After phacofragmentation and surface modification, the final average size of the carbon nanotubes was approximately 50 nm (Fig. 1c). The uptake assay was performed by incubating FITC/PEG-conjugated carbon nanotubes with NCI-H460, a human lung cancer cell line, and subsequently visualizing cell distribution via confocal microscopy. The images confirmed that the nanotubes were mostly internalized or strongly adhered to the cell surface within four hours following the incubation (Fig. 1d). We next performed cell viability assays using CCK-8 kit to examine the anti-cancer effect of laser irradiation and carbon nanotubes in vitro. As illustrated in Fig. 1e, incubating the cells with carbon nanotubes in the absence of laser exposure did not induce apoptosis (P = 0.021). On the other hand, the cancer cells incubated with carbon nanotubes showed reduced viability only when subjected to laser treatment, as indicated by the sharp decrease of fluorescence at 450 nm. (P = 0.021, Fig. 1f).

View Article: PubMed Central - PubMed

ABSTRACT

The prevalence of cardiac malignant neoplasms in the general population has been shown to be significant higher than what was previously estimated, yet their treatment has remained difficult and effective therapies are lacking. In the current study, we developed a novel thermotherapy in which PEG-functionalized carbon nanotubes were injected into the tumor regions to assist in the targeted delivery of infrared radiation energy with minimal hyperthermic damage to the surrounding normal tissues. In a mouse model of cardiac malignant neoplasms, the injected carbon nanotubes could rapidly induce coagulative necrosis of tumor tissues when exposed to infrared irradiation. In accordance, the treatment was also found to result in a restoration of heart functions and a concomitant increase of survival rate in mice. Taken together, our carbon nanotube-based thermotherapy successfully addressed the difficulty facing conventional laser ablation methods with regard to off-target thermal injury, and could pave the way for the development of more effective therapies against cardiac malignant neoplasms.

No MeSH data available.


Related in: MedlinePlus